Population pharmacokinetics of etoposide: application to therapeutic drug monitoring.

Antineoplastic agent etoposide (VP16) displays narrow therapeutic index and erratic pharmacokinetics, and dose individualization is a convenient way for overcoming the interpatient variability, so as to maintain the drug exposure within a therapeutic range. The authors proposed a population-based Bayesian methodology to adjust routinely VP16 dosage when given as a 5-day infusion. The mean VP16 pharmacokinetic parameters of the reference population calculated from 14 patients following the two-stage method were CL = 1.92 +/- 0.512 L/h and t(1/2) = 6.7 +/- 2 hours. The reference population was next used prospectively for Bayesian dose individualization for 25 patients (47 courses) undergoing 5-day infusions of VP16. Resulting steady-state concentrations proved to be successfully adjusted to the target values in 77% of the courses. Therefore, the method presented here meets the requirements for routine therapeutic drug monitoring of VP16, a major anticancer drug extensively used in clinical oncology.